title: Sex differences in the effect of cytochrome P450 2C19 polymorphisms on the risk of diabetic retinopathy: a retrospective longitudinal study in Japanese patients with type 2 diabetes.
abstract: Cytochrome P450 2C19 (CYP2C19) is expressed in human endothelial cells and catalyzes the biosynthesis of vasoprotective epoxyeicosatrienoic acids and 19-hydroxyeicosatetraenoic acid from arachidonic acid. This study investigated the association between CYP2C19 polymorphisms and an increased risk of diabetic retinopathy (DR). A clinic-based retrospective longitudinal analysis was carried out that included 383 Japanese patients with type 2 diabetes mellitus. Compared with male extensive metabolizers, female intermediate metabolizers [adjusted odds ratio (OR), 2.43; 95% confidence interval (95% CI), 1.17-5.06] and poor metabolizers (OR, 7.49; 95% CI, 2.64-21.26) were at a significantly higher risk of developing DR. Furthermore, the CYP2C19 poor metabolizer genotype was found to be an independent risk factor for DR only in women when patients were stratified by sex (OR, 4.18; 95% CI, 1.42-12.26). This is the first report showing the interactive effect of sex and CYP2C19 polymorphisms on microvascular disease in humans, although further investigations are needed to verify these findings.
authors.affiliation: aDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences bCenter for Clinical Pharmaceutical Sciences, Kumamoto University cJinnouchi Clinic, Diabetes Care Center, Kumamoto, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Kajiwara
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.forename: Ayana
authors.initials: A
authors.lastname: Kita
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kamihashi
authors.forename: Haruna
authors.initials: H
authors.lastname: Miyagawa
authors.forename: Misaki
authors.initials: M
authors.lastname: Sakata
authors.forename: Madoka
authors.initials: M
authors.lastname: Noai
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19